It has been demonstrated in this laboratory that corticoid isoproterenol interaction consistenly elicits severe ventricular rhythm disorders terminating in ventricular fibrillation and death in the albino rat. This species is otherwise very resistant to isoproterenol. As a result of this interaction with corticoid, the acute toxicity of isoproterenol in the rat is increased by 47,000 times and by 320,000 times with the further addition of aminophylline. Myocardial sensitization to isoproterenol by corticoid pretreatment is inhibited by the protein synthesis inhibitors such as cycloheximide and actinomycin D. In view of the enormous potentiation brought about by such a drug-drug interaction, which may have played a contributory role in the "death epidemic" among patients with bronchial asthma in the British Commonwealth some years ago, it is proposed (1) to continue the investigation of various combinations of corticosteroids and sympathomimetics for the purpose of determining their comparative propensity for triggering dangerous dysrhythmias, and (2) to elucidate the factors in corticosteroid-beta adrenergic agonist interaction which facilitate the emergence of ventricular fibrillation. The investigation will encompass acute and chronic experiments in awake rats and dogs, in which blood pressure and ECG may be monitored and which have been treated for various periods of time with corticoids. It is anticipated that the methodology employed may aid in uncovering potentially cardiotoxic drug-drug interactions and may help in elucidating the mechanism involved in this phenomenon.